Increased ß-adrenergic stimulation augments vascular smooth muscle cell calcification via PKA/CREB signalling.
Pflugers Arch
; 473(12): 1899-1910, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34564739
ABSTRACT
In chronic kidney disease (CKD), hyperphosphatemia promotes medial vascular calcification, a process augmented by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). VSMC function is regulated by sympathetic innervation, and these cells express α- and ß-adrenergic receptors. The present study explored the effects of ß2-adrenergic stimulation by isoproterenol on VSMC calcification. Experiments were performed in primary human aortic VSMCs treated with isoproterenol during control or high phosphate conditions. As a result, isoproterenol dose dependently up-regulated the expression of osteogenic markers core-binding factor α-1 (CBFA1) and tissue-nonspecific alkaline phosphatase (ALPL) in VSMCs. Furthermore, prolonged isoproterenol exposure augmented phosphate-induced calcification of VSMCs. Isoproterenol increased the activation of PKA and CREB, while knockdown of the PKA catalytic subunit α (PRKACA) or of CREB1 genes was able to suppress the pro-calcific effects of isoproterenol in VSMCs. ß2-adrenergic receptor silencing or inhibition with the selective antagonist ICI 118,551 blocked isoproterenol-induced osteogenic signalling in VSMCs. The present observations imply a pro-calcific effect of ß2-adrenergic overstimulation in VSMCs, which is mediated, at least partly, by PKA/CREB signalling. These observations may support a link between sympathetic overactivity in CKD and vascular calcification.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
Proteínas Quinasas Dependientes de AMP Cíclico
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Adrenérgicos
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Miocitos del Músculo Liso
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Calcificación Vascular
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Músculo Liso Vascular
Límite:
Humans
Idioma:
En
Revista:
Pflugers Arch
Año:
2021
Tipo del documento:
Article
País de afiliación:
Austria